As many of the traditional mood stabilizers used to treat bipolar disorder, including lithium and valproic acid, carry some teratogenic risk and the reproductive safety of other medications, including the atypical antipsychotic agents, has not been well-characterized, many women with bipolar disorder decide to discontinue their treatment during pregnancy. A new study from Dr. Adele Viguera and her colleagues at the Massachusetts General Hospital and the Emory University School of Medicine helps to better define the risks associated with discontinuing treatment during pregnancy.
The study followed 89 women with bipolar disorder (69% type I, 31% type II) prospectively across pregnancy. Pregnant women (prior to 24 weeks gestation) were eligible for the study if they 1) were euthymic for at least 1 month prior to conception, 2) were receiving treatment with a mood stabilizer, or 3) had discontinued pharmacotherapy no more than 6 months prior to pregnancy or within the first trimester. Most subjects (>70%) were taking more than one psychotropic medication, typically a mood stabilizer in combination with an antidepressant and/or antipsychotic agent. This was a naturalistic study, and based on the recommendations of their own treaters, women elected either to maintain (n=62) or to discontinue (n=27) treatment with a mood stabilizer.
During the course of pregnancy, 70.8% of the participants experienced at least one mood episode. Most of these episodes were either depressive or mixed (74%), and 47% occurred during the first trimester. The risk of recurrence was significantly higher in women who discontinued treatment with mood stabilizers (85.5%) than those who maintained treatment (37.0%). In addition, the women who discontinued mood stabilizer spent over 40% of their pregnancy in an illness episode, versus only 8.8% among subjects who maintained treatment with a mood stabilizer.
The investigators also examined whether certain demographic or clinical variables were associated with increased risk of recurrence during pregnancy. The only pregnancy-related predictor of relapse was unplanned pregnancy. Clinical variables associated with a higher risk of recurrence included younger age at illness onset (RR=1.6), bipolar II disorder diagnosis (RR=1.5), history of rapid cycling (RR=1.5), history of mixed episodes (RR=1.5) and shorter duration of clinical stability since last episode (RR=1.5). Treatment factors associated with increased relapse rates included polytherapy with more than two psychotropic agents (RR=2.3), use of antidepressants (RR=2.0), primary mood stabilizer other than lithium (RR=1.6), and abrupt discontinuation (less than two weeks) of mood stabilizer (RR=1.4).
While this study has some limitations, it is the largest prospective study of the course of bipolar disorder during pregnancy to date and yields important data which can help to inform the treatment of bipolar illness during pregnancy. The study indicates that the risk of recurrent illness during pregnancy is extremely high, particularly when medications were discontinued. While the authors acknowledge that these findings may not generalize to other clinical populations as the study was conducted with subjects seen in a specialty research program, the findings clearly indicate that women with more severe or recurrent illness are at greatest risk for recurrent illness.
Consistent with a similar prospective study carried out in women with unipolar depression (Cohen et al, 2006), this study demonstrates that discontinuation of ongoing maintenance treatment in women with bipolar disorder carries a very high risk of recurrent illness. In short, pregnancy does not appear to be protective against psychiatric illness. Although there may be concerns regarding the use of psychotropic medications during pregnancy, these findings challenge the common practice of abruptly discontinuing maintenance treatment for bipolar disorder during pregnancy.
Ruta Nonacs, MD PhD
Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, et al. Risk of Recurrence in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood Stabilizer Discontinuation. Am J Psychiatry 2007; 164:1817-1824.
Comments from Dr. Marlene Freeman
Medscape Interview With Dr. Adele Viguera
This study has helped me a lot. I have been searching the net high and low for information regarding this subject. Im bipolar type II my husband and I want to have a child. I am fearful of what to do. I am glad that someone out there cared enough to do a study like this one. Thank you!
I also want to extend my thanks. Like Neyka, I have bipolar II and want to have a child. I’ve gone to multiple doctors for guidance and no one has been able to give me any good information, and there really isn’t that much out there on the net. This is SOOO helpful. I wish more ob/gyns were familiar with this information.
I have Bipolar and would like to plan a family. I would be interested in and support further research with respect to keeping on medication and which medications offer the lowest risk to a developing embryo. Furthermore I would love to breastfeed my future baby but am having difficulty finding a med. that is not passed on through breast-milk.
@Pam, Unfortunately all medications are passed into the breast milk. The concentrations of these medications vary, as do the potential risks associated with each medication.
Here are some articles on our site that discuss breastfeeding and the mood stabilizers lithium and lamotrigine:
Me again! I wrote a comment (above) about 8 months ago thanking you for all this information. After bringing the articles to my dr we decided to continue my meds and adjust them to the lowest possible dose I could tolerate while my husband and I were ttc. The adjustments were finished in August, and I went in for a blood test today to confirm pregnancy! Assuming I am pregnant (6 weeks) my dr suggested I contact you guys to see if you take patients with bipolar to help monitor them during pregnancy (i live near worcester, ma) or if you have a consultation # that she can call during my pregnancy to guide my treatment. She is reading up on the literature, but she thinks having experts involved might be beneficial to me and the baby. Thanks!
Wondering what are the safest mood stabilisers in pregnancy and breast feeding? Currently using seroquel and ineffective